公开(公告)号：US20110262454A1

公开(公告)日：2011-10-27

申请号：US13069705

申请日：2011-03-23

申请人： Peter U. PARK ,  Laura BARTLE ,  Anna SKALETSKAYA ,  Viktor GOLMAKHER ,  Daniel TAVARES ,  Jutta DECKERT ,  Vincent MILOL ,  Veronique BLANC

发明人： Peter U. PARK ,  Laura BARTLE ,  Anna SKALETSKAYA ,  Viktor GOLMAKHER ,  Daniel TAVARES ,  Jutta DECKERT ,  Vincent MILOL ,  Veronique BLANC

IPC分类号： A61K39/395 ,  C12N15/85 ,  C12N5/10 ,  C07K16/40 ,  A61P35/00 ,  C07H21/04 ,  A61P19/02 ,  A61P1/00 ,  A61P1/04 ,  A61P25/00 ,  A61P11/06 ,  G01N33/574 ,  A61P35/02

CPC分类号： G01N33/57426 ,  A61K47/6803 ,  A61K47/6867 ,  A61K2039/505 ,  C07K16/2896 ,  C07K16/462 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  G01N33/57484 ,  G01N2333/924

摘要： Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38+ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

摘要翻译： 与CD38特异性结合的抗体，人源化抗体，表面抗体，抗体片段，衍生化抗体和与细胞毒性剂的缀合物能够通过细胞凋亡，抗体依赖性细胞介导的细胞毒性（ADCC）和/ 或补体依赖性细胞毒性（CDC）。 所述抗体及其片段可用于治疗表达CD38蛋白的肿瘤，例如多发性骨髓瘤，慢性淋巴细胞性白血病，慢性骨髓性白血病，急性骨髓性白血病或急性淋巴细胞白血病，或治疗自身免疫性和炎性疾病如 系统性红斑狼疮，类风湿关节炎，多发性硬化症，红斑狼疮和哮喘。 所述衍生化抗体可用于表达CD38水平升高的肿瘤的诊断和成像。 还提供了包含细胞结合剂和细胞毒性剂的细胞毒性缀合物，包含缀合物的治疗组合物，用于抑制细胞生长和治疗疾病的方法以及包含细胞毒性缀合物的试剂盒。 特别地，细胞结合剂是识别并结合CD38蛋白的单克隆抗体及其表位结合片段。